This proposal will investigate the specific role of platelet leukocyte interactions as a mediator of normal leukocyte function during bacterial infection. Mice with the Chediak Higashi syndrome will be used for this work since both defective platelets and impared leukocyte function are present. The relationship between platelet serotonin and normal leukocyte function can be evaluated through studies which replace the missing serotonin and through the use of other substances which may affect the leukocyte cyclic nucleotide balance in a similar manner. In vitro studies will measure leukocyte bacterial killing and cyclic nucleotide effects in the presence and absence of these substances or after the parenteral administration. In vivo studies will evaluate for increased resistance to the effect of experimental infection. The specificity of platelet serotonin and an evaluation of serotonin metabolites also will be determined. A necessary role for platelets as mediators of host defense has not been previously demonstrated. The chediak-Higashi anomaly suggests the requirement for this interaction. Our studies will address this point and will lead to a better understanding of the controlling mechanisms of leukocyte function.